Variant rs11542040 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_000041.4(APOE):c.304C>A(p.Pro102Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P102R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

APOE
NM_000041.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.50

Variant links:

Genes affected

APOE (HGNC:613): (apolipoprotein E) The protein encoded by this gene is a major apoprotein of the chylomicron. It binds to a specific liver and peripheral cell receptor, and is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. This gene maps to chromosome 19 in a cluster with the related apolipoprotein C1 and C2 genes. Mutations in this gene result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants. [provided by RefSeq, Jun 2016]

APOE links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.8

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOE	NM_000041.4 linkuse as main transcript	c.304C>A	p.Pro102Thr	missense_variant	4/4	ENST00000252486.9	NP_000032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
APOE	ENST00000252486.9 linkuse as main transcript	c.304C>A	p.Pro102Thr	missense_variant	4/4	1	NM_000041.4	ENSP00000252486	P1
APOE	ENST00000425718.1 linkuse as main transcript	c.304C>A	p.Pro102Thr	missense_variant	3/3	1		ENSP00000410423
APOE	ENST00000434152.5 linkuse as main transcript	c.382C>A	p.Pro128Thr	missense_variant	4/4	2		ENSP00000413653
APOE	ENST00000446996.5 linkuse as main transcript	c.304C>A	p.Pro102Thr	missense_variant	4/4	2		ENSP00000413135

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460616

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726602

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.070

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

D;T;.;.

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.055

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.85

T;T;T;T

M_CAP

Pathogenic

0.51

MetaRNN

Pathogenic

0.80

D;D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.3

M;.;.;.

MutationTaster

Benign

0.76

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-6.7

D;D;.;D

REVEL

Uncertain

0.57

Sift

Uncertain

0.0020

D;D;.;D

Sift4G

Uncertain

0.027

D;D;D;D

Polyphen

0.99

D;.;.;.

Vest4

0.62

MutPred

0.58

Gain of phosphorylation at P102 (P = 0.0241);Gain of phosphorylation at P102 (P = 0.0241);.;Gain of phosphorylation at P102 (P = 0.0241);

MVP

0.99

MPC

1.7

ClinPred

0.91

GERP RS

4.3

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.63

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over